Autologous bone marrow transplantation was performed in lethally irradiated beagles of the Cooperstown colony at different time intervals prior to or after kidney transplantation, using donors of identical DLA haplotypes and pedigree. A group of 21 recipients was transplanted with kidneys 20 hrs prior to removal of marrow and irradiation. Only 3 dogs remained unresponsive to the renal allografts (3 years or more). Seven recipients accorded intermediate survival times (56-667 days) and 8 transplants were rejected before 50 days. When kidney transplantation was performed at the time of marrow replacement, 25% of the recipients continued to have normal function for more than 2.5 years; the rest were rejected within 98 days. The best survival rate was found when the kidneys were transplanted 12 to 36 hrs after lethal irradiation and autologous bone marrow replacement (3 groups - 12 hrs, 24 hrs, and 36 hrs). Sixty-two percent of the transplanted dogs in these groups currently survive with normal renal function at present. If the kidney was transplated immediately after irradiation, but bone marrow replacement was done 40 hrs later, only 26% of the transplanted dogs developed normal renal function (60-950 days). To test whether the surviving recipients in the above groups developed tolerance toward other tissues of their donor, the survivors received skin grafts from the kidney donor and from DLA identical dogs. In approximately 50% of the cases, the recipients failed to reject skin from the kidney donors with one exception, they rejected skin from another DLA identical donor. The rest of the kidney donors rejected skin from their kidney donor. These dogs were also able to muster accelerated rejection responses to second and third set skin grafts from the same donor. Thus in 50% of the cases, the kidney transplants induced tolerance to kidney only, but not to skin from the same source - i.e., split tolerance. These studies established the time parameters for successful autologous marrow replacement in relation to kidney transplantation and irradiation, and the immunologic specificity of the resulting tolerogenic state in large adult mammals.